Metabolic and toxicological considerations for phosphoinositide 3-kinase delta inhibitors in the treatment of chronic lymphocytic leukemia.

IF 3.9 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Expert Opinion on Drug Metabolism & Toxicology Pub Date : 2023-09-01 Epub Date: 2023-09-15 DOI:10.1080/17425255.2023.2260305

Magdalena Witkowska, Agata Majchrzak, Paweł Robak, Anna Wolska-Washer, Tadeusz Robak

{"title":"Metabolic and toxicological considerations for phosphoinositide 3-kinase delta inhibitors in the treatment of chronic lymphocytic leukemia.","authors":"Magdalena Witkowska, Agata Majchrzak, Paweł Robak, Anna Wolska-Washer, Tadeusz Robak","doi":"10.1080/17425255.2023.2260305","DOIUrl":null,"url":null,"abstract":"Introduction: Phosphoinositide 3-kinase delta (PI3Kδ) inhibitors are a class of novel agents that are mainly used to treat B-cell malignancies. They function by inhibiting one or more enzymes which are part of the PI3K/AKT/mTOR pathway. Idelalisib is a first-in-class PI3Kδ inhibitor effective in patients with B-cell lymphoid malignancies.Areas covered: This article reviews the chemical structure, mechanism of action, and metabolic and toxicological properties of PI3Kδ inhibitors and discusses their clinical applications in monotherapy and in combination with other agents for the treatment of chronic lymphocytic leukemia (CLL). A search was conducted of PubMed, Web of Science, and Google Scholar for articles in English.Results/conclusion: PI3Kδ inhibitors hold potential for the treatment of B-cell malignancies, including CLL. However, their use is also associated with severe toxicities, including pneumonia, cytopenias, hepatitis, and rash. Newer drugs are in development to reduce toxicity with novel schedules and/or combinations.Expert opinion: The development of novel PI3Kδ inhibitors might help to reduce toxicity and improve efficacy in patients with CLL and other B-cell lymphoid malignancies.","PeriodicalId":12250,"journal":{"name":"Expert Opinion on Drug Metabolism & Toxicology","volume":" ","pages":"617-633"},"PeriodicalIF":3.9000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Opinion on Drug Metabolism & Toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17425255.2023.2260305","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/15 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: Phosphoinositide 3-kinase delta (PI3Kδ) inhibitors are a class of novel agents that are mainly used to treat B-cell malignancies. They function by inhibiting one or more enzymes which are part of the PI3K/AKT/mTOR pathway. Idelalisib is a first-in-class PI3Kδ inhibitor effective in patients with B-cell lymphoid malignancies.

Areas covered: This article reviews the chemical structure, mechanism of action, and metabolic and toxicological properties of PI3Kδ inhibitors and discusses their clinical applications in monotherapy and in combination with other agents for the treatment of chronic lymphocytic leukemia (CLL). A search was conducted of PubMed, Web of Science, and Google Scholar for articles in English.

Results/conclusion: PI3Kδ inhibitors hold potential for the treatment of B-cell malignancies, including CLL. However, their use is also associated with severe toxicities, including pneumonia, cytopenias, hepatitis, and rash. Newer drugs are in development to reduce toxicity with novel schedules and/or combinations.

Expert opinion: The development of novel PI3Kδ inhibitors might help to reduce toxicity and improve efficacy in patients with CLL and other B-cell lymphoid malignancies.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

磷酸肌醇3-激酶δ抑制剂治疗慢性淋巴细胞白血病的代谢和毒理学考虑。

简介：磷脂酰肌醇3-激酶δ（PI3Kδ）抑制剂是一类主要用于治疗B细胞恶性肿瘤的新型药物。它们通过抑制一种或多种作为PI3K/AKT/mTOR途径一部分的酶发挥作用。Idelalisib是第一种对B细胞淋巴系统恶性肿瘤患者有效的PI3Kδ抑制剂。涵盖领域：本文综述了PI3Kδ抑制剂的化学结构、作用机制、代谢和毒理学特性，并讨论了它们在单药治疗和与其他药物联合治疗慢性淋巴细胞白血病（CLL）中的临床应用。在PubMed、Web of Science和Google Scholar上搜索英文文章。结果/结论：PI3Kδ抑制剂具有治疗B细胞恶性肿瘤（包括CLL）的潜力。然而，它们的使用也与严重的毒性有关，包括肺炎、细胞减少、肝炎和皮疹。正在开发新的药物，以通过新的方案和/或组合来降低毒性。专家意见：开发新型PI3Kδ抑制剂可能有助于降低CLL和其他B细胞淋巴系统恶性肿瘤患者的毒性并提高疗效。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Expert Opinion on Drug Metabolism & Toxicology 医学-生化与分子生物学

CiteScore

7.90

自引率

2.30%

发文量

审稿时长

4-8 weeks

期刊介绍： Expert Opinion on Drug Metabolism & Toxicology (ISSN 1742-5255 [print], 1744-7607 [electronic]) is a MEDLINE-indexed, peer-reviewed, international journal publishing review articles on all aspects of ADME-Tox. Each article is structured to incorporate the author’s own expert opinion on the scope for future development. The Editors welcome: Reviews covering metabolic, pharmacokinetic and toxicological issues relating to specific drugs, drug-drug interactions, drug classes or their use in specific populations; issues relating to enzymes involved in the metabolism, disposition and excretion of drugs; techniques involved in the study of drug metabolism and toxicology; novel technologies for obtaining ADME-Tox data. Drug Evaluations reviewing the clinical, toxicological and pharmacokinetic data on a particular drug. The audience consists of scientists and managers in the pharmaceutical industry, pharmacologists, clinical toxicologists and related professionals.